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Molecular Basis for Resistance of Acanthamoeba Tubulins to All Major Classes of Antitubulin Compounds ^,

Fiona L. Henriquez,^1* Paul R. Ingram,¹ Stephen P. Muench,^2, David W. Rice,² and Craig W. Roberts¹

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom,¹ Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom²

Received 16 March 2007/ Returned for modification 22 July 2007/ Accepted 27 November 2007

Tubulin is essential to eukaryotic cells and is targeted by several antineoplastics, herbicides, and antimicrobials. We demonstrate that Acanthamoeba spp. are resistant to five antimicrotubule compounds, unlike any other eukaryote studied so far. Resistance correlates with critical amino acid differences within the inhibitor binding sites of the tubulin heterodimers.

Published ahead of print on 10 December 2007.

Supplemental material for this article may be found at http://aac.asm.org/.

Present address: Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.